Capsid-like particles decorated with the SARS2-CoV-2 receptor-binding domain elicit strong virus neutralization activity

Abstract The rapid development of a SARS-CoV-2 vaccine is a global priority. Here, we developed two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. RBD antigens were displayed on AP205 CLPs through a novel split-protein Tag/Catcher ensuring unidirectional and high-density display of RBD. Both soluble recombinant RBD, and RBD displayed on CLPs bound the ACE2 receptor with nanomolar affinity. Mice were vaccinated with soluble RBD or CLP-displayed RBD, formulated in Squalene-Water-Emulsion. The RBD-CLP vaccines induced higher levels of serum anti-RBD antibodies, than the soluble RBD vaccines. Remarkably, one injection with our lead RBD-CLP vaccine in mice elicited virus neutralization antibody titers comparable to those found in patients which had recovered from Covid-19. Following booster vaccinations, the virus neutralization titers exceeded those measured after natural infection, at serum dilutions above 1:10.000. Thus, the RBD-CLP vaccine is highly promising candidates for preventing COVID-19 disease.